Outline the role of a thick myosin filament from skeletal muscle during muscle contraction.
- Myosin binds to active sites on the actin molecules to from cross-bridges
- Attached to the rod portion by a hinge region that can bend and straighten during contraction
- Have ATPase activity: activity that breaks down ATP, releasing energy - part of the energy is used to bend the hinge region of the myosin molecule during contraction.
Draw and label thick myosin filament
A = Rod
B = Head
C = Coiled portion of the two alpha-helices
D = Light chains
E = Two heavy chains
F = Hinge region
Explain terms weak and bronsted-lowry acid.
Weak acid - partially dissociates in water
Bronsted-lowry = proton donor
Describe the advantages and disadvantages of the topical gel compared to oral tablets.
- Local administration therefore localised effect and better targeting
- Avoids hepatic first-pass metabolism
- Lower effective dose, lower risk of systemic adverse effects
- Variable dosing - unit dose more difficult to measure compared to tablets which allows uniform dosing
- Less practical if to be administered to a large surface area
Compare innate and adaptive immunity.
Innate/Adaptive
Rapid/Slow
No memory/Memory
Fixed/Variable
Limited specificity/Highly specific
Constant during response/Improves during response
Explain what competitive antagonism means?
- Competitive antagonist binds to receptor at the same binding site as the agonist
- But without activating the receptor
- Agonst and antagonist ‘compete’ for the same binding site on the receptor
- Once bound an antagonist will block agonist binding
Describe the key events of a Gq signal transduction pathway.
- The binding of the ligand to the Gq protein receptor causes a conformational change in the associated Gq protein that induce the exchange of GDP with GTP and the liberation of the alpha subunit of the Gq protein.
- The Gq alpha sub unit stimulates the enzyme phospholipase C which cleaves PIP2 into second messengers IP3 and DAG
- IPS which is water soluble will travel through the cytosol to stimulate calcium release from the ER.
- Calcium ions bind to CaM, Ca2+-CaM complex activates CaM kinases which phosphorylate a number of proteins leading to a cellular response.
- The second messenger DAG is hydrophobic remains in the membrane where it can increase the activity of Ca2+ dependent kinases and evoke a cellular response by activating PKC
Explain the concept of drug-receptor interaction that refers to the ‘lock and key’ model.
A receptor structure that has a region with a particular shaped pocket at which an appropriately shaped molecule can interact.
How does the lock and key concept differ from the induced fit?
Induced fit states morphology is not necessarily complementary to the conformation of ligand.
As the drug approaches the receptor the receptor alters the conformation of its binding site to produce drug-receptor complex
List the main disadvantages associated with eye drops.
- Drug instability compared to the solid state
- A number of drugs are poorly soluble in water
- Liquids are bulky compared to the solid dosage form
- Liquids frequently require cold storage
- Packaging costs are often higher for liquids
Outline 4 properties of a powder mixture that may affect the dose uniformity of tablets.
- Powder flowability - critical for uniform filling of die
- Particle size - may affect powder flow and extent of mixing/segregation
- Particle shape - may affect flowability and compactability
- Absorbed moisture content - may affect flowability and compatibility
Explain what is meant by the term ‘prodrug’?
Inactive medication that, that after administration is metabolised into the pharmacologically active drug.
Why is the salt form the preferred form for oral administration?
As ionic, the amine salt is more soluble in water than the parent amine - readily dissolves in GI tract after breakdown of formulation, enhancing absorption.
Describe the function and secretions of the four main cell types located within the islets of Langerhans of the endocrine pancreas.
- Beta cells which secrete insulin - stimulates glycogen, protein and fatty acid synthesis, facilitates glucose uptake and lowers blood glucose
- Alpha cells which secrete glucagon - generally opposite to insulin, increased blood glucose
- delta cells which secrete somatostatin - locally acting hormone inhibits other endocrine cells
- PP/F cells which secrete pancreatic polypeptide - stimulates gastric chief cells, inhibits bile secretions and inhibit pancreatic exocrine function
Describe the events of the immune response happening in the first four days.
- We have an immediate and induced immune response towards virus.
- Immediate innate immune response lasts for the first 4 hours and includes physical and chemical barriers, release of peptides and activation of complement.
- After 4 hours and until 4 days the induced innate immune response kicks in.
- This includes activation of toll-like receptors in the effected cells
- Which activate signal transduction pathways leading to release of type 1 interferon.
- Interferon activates NK ells
- Which kill virus infected cells by inducing apoptosis
- Induced innate immune system also causes the release of cytokines and inflammation
- And the activation of phagocytosis mediated by macrophages and neutrophils.
